Rabphilin-3A

A multifunctional regulator of synaptic vesicle traffic

Marie E Burns, T. Sasaki, Y. Takai, G. J. Augustine

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

We have investigated the function of the synaptic vesicle protein Rabphilin-3A in neurotransmitter release at the squid giant synapse. Presynaptic microinjection of recombinant Rabphilin-3A reversibly inhibited the exocytotic release of neurotransmitter. Injection of fragments of Rabphilin-3A indicate that at least two distinct regions of the protein inhibit neurotransmitter release: the NH2-terminal region that binds Rab3A and is phosphorylated by protein kinases and the two C2 domains that interact with calcium, phospholipid, and β-adducin. Each of the inhibitory fragments and the full-length protein had separate effects on presynaptic morphology, suggesting that individual domains were inhibiting a subset of the reactions in which the full-length protein participates. In addition to inhibiting exocytosis, constructs containing the NH2 terminus of Rabphilin-3A also perturbed the endocytotic pathway, as indicated by changes in the membrane areas of endosomes, coated vesicles, and the plasma membrane. These results indicate that Rabphilin-3A regulates synaptic vesicle traffic and appears to do so at distinct stages of both the exocytotic and endocytotic pathways.

Original languageEnglish (US)
Pages (from-to)243-255
Number of pages13
JournalJournal of General Physiology
Volume111
Issue number2
DOIs
StatePublished - Feb 1998
Externally publishedYes

Fingerprint

Synaptic Vesicles
Neurotransmitter Agents
Proteins
Coated Vesicles
Decapodiformes
Endosomes
Exocytosis
Microinjections
Synapses
Protein Kinases
Phospholipids
Cell Membrane
rabphilin-3A
Calcium
Injections
Membranes

Keywords

  • Endocytosis
  • Exocytosis
  • GTP-binding proteins
  • Neurotransmitter release
  • Rabs

ASJC Scopus subject areas

  • Physiology

Cite this

Rabphilin-3A : A multifunctional regulator of synaptic vesicle traffic. / Burns, Marie E; Sasaki, T.; Takai, Y.; Augustine, G. J.

In: Journal of General Physiology, Vol. 111, No. 2, 02.1998, p. 243-255.

Research output: Contribution to journalArticle

Burns, Marie E ; Sasaki, T. ; Takai, Y. ; Augustine, G. J. / Rabphilin-3A : A multifunctional regulator of synaptic vesicle traffic. In: Journal of General Physiology. 1998 ; Vol. 111, No. 2. pp. 243-255.
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